Ventricular tachycardia mechanisms

Reentry mechanism Intranodal (AV node) reentry Extranodal reentry Reentrant tachyarrhythmia Atrial flutter Atrial fibrillation Ventricular tachycardia Ventricular fibrillation Conduction B/ocks ... 

Procainamide (Class IA antiarrhythmic drug) is an effective agent for ventricular tachycardia. Its mechanism of action involves blockade of the fast Na+ channels responsible for phase 0 in the fast response tissue of the ventricles. Therefore, its effect is most pronounced in the Purkinje fibers. The effects of this drug s activity include a decrease in excitability of myocardial cells and in conduction velocity. Therefore, a decrease in the rate of the phase 0 upstroke and a prolonged repolarization are observed. As a result, duration of the action potential and the associated refractory period is prolonged and the heart rate is reduced. These effects are illustrated by an increase in the duration of the QRS complex. 

Mechanism of Action An antiarrhythmic that directly affects myocardial cell membranes. Therapeutic Effect Contributes to suppression of ventricular tachycardia. Pharmacokinetics Absorption is not expected to be present in peripheral blood at recommended doses. Protein binding l%-6%. Not metabolized. Excreted unchanged in urine. Removed by hemodialysis. Half-life 6-13.5 hr. 

Adenosine is a nucleoside that occurs naturally throughout the body. Its half-life in the blood is less than 10 seconds. Its mechanism of action involves activation of an inward rectifier K+ current and inhibition of calcium current. The results of these actions are marked hyperpolarization and suppression of calcium-dependent action potentials. When given as a bolus dose, adenosine directly inhibits atrioventricular nodal conduction and increases the atrioventricular nodal refractory period but has lesser effects on the sinoatrial node. Adenosine is currently the drug of choice for prompt conversion of paroxysmal supraventricular tachycardia to sinus rhythm because of its high efficacy (90-95%) and very short duration of action. It is usually given in a bolus dose of 6 mg followed, if necessary, by a dose of 12 mg. An uncommon variant of ventricular tachycardia is adenosine-sensitive. The drug is less effective in the presence of adenosine receptor blockers such as theophylline or caffeine, and its effects are potentiated by adenosine uptake inhibitors such as dipyridamole. 

Make a firm diagnosis. A firm arrhythmia diagnosis should be established. For example, the misuse of verapamil in patients with ventricular tachycardia mistakenly diagnosed as supraventricular tachycardia can lead to catastrophic hypotension and cardiac arrest. As increasingly sophisticated methods to characterize underlying arrhythmia mechanisms become available and are validated, it may be possible to direct certain drugs toward specific arrhythmia mechanisms. 

Saoudi N, Galtier M, Hidden F, Gerber L, Letac B. Bundle-branch reentrant ventricular tachycardia a possible mechanism of flecainide proarrhythmic effect. J Electrophysiol 1988 2 365-71. 

A synergistic interaction of intrathecal fentanyl 100 pg and morphine 0.5 mg, given before induction, with systemically administered lidocaine 200 mg 4 hours later for ventricular tachycardia, resulted in potentiation of opioid effects in a 74-year-old man with major heart disease after coronary artery bypass grafting during the 5 minutes after lidocaine he had a respiratory arrest with loss of consciousness and miotic pupils, all reversed by naloxone (80). The proposed mechanism was thought to be a reduction in calcium ion concentrations in opioid-sensitive CNS sites. 

Amiodarone is indicated for the suppression and prevention of documented life-threatening, recurrent, ventricular tachycardia or fibrillation when other agents have failed. Amiodarone is also used in the management of supraventricular tachyarrhythmias including paroxysmal atrial fibrillation and atrial flutter, ectopic or multifocal atrial tachycardia, junctional tachycardia, and paroxysmal reentrant supraventricular tachycardia when other agents have failed to suppress or prevent their recurrence. Amiodarone has also been used to treat wide-complex tachycardia of uncertain mechanism. 

ANTIARRHYTHMIC agents (Class I agents, e.g. disopyramide, flecainide. lignocaine. procainamide, quinidine) are sodium-channel blockers and are mainly used to treat atrial and ventricular tachycardias (see antiarrhythmic agents). ANTIEPILEPTICS have a number of mechanisms of action, but some appear to have a component involving modulation of sodium-channel function, e.g. carbamaxepine and phenytoin (see anticonvulsants). 

Disopyramide, proprietary name Norpace, is used for maintenance of sinus rhythm in patients with atrial flutter and atrial fibrillation and for prevention of ventricular tachycardia and fibrillation. The mechanism of action of disopyramide is similar to that of quinidine, and the drug can be used as replacement therapy for quinidine when quinidine side effects are intolerable. 

Procainamide, proprietary name Pronestyl, is used for therapy of PVCs, ventricular tachycardia, atrial fibrillation, and paroxysmal atrial tachycardia. Its mechanism of action is similar to that of quinidine in that it increases the threshold membrane potential by blocking potassium outflow, reducing excitability and contraction velocity in Purkinje s fibers and ventricular muscle. 

A potential case of an interaction between quinidine and flucloxacillin was demonstrated in a 63-year-old patient with recently diagnosed dilated cardiomyopathy who was admitted to the hospital with polymorphic ventricular tachycardia and ventricular fibrillation episodes induced by bradycardia. The patient was on a heart failure regimen of furosemide, spironolactone and perindopril, and was initiated on oral quinidine in the hospital for the prevention of ventricular arrhythmias. The patient s temporary pacemaker lead was removed and an implantable cardioverter-defibrillator was placed due to continued ventricular fibrillation. The next day, the patient became febrile. Culture of pacemaker lead tip and blood cultures were positive for S. aureus. Flucloxacillin and rifampin were initiated, but rifampin was discontinued due to the development of renal insufficiency and liver test abnormalities. These were normalised after rifampin was discontinued. The patient required continuous pacing to prevent ventricular tachycardia episodes, and quinidine was increased to 2800 mg per day (maximum daily dose). Quinidine plasma levels were subtherapeutic at 1.1 mg/L. The authors speculate that this interaction was due to quinidine being a substrate of Pgp and CYP3A4, and flucloxacillin s ability to induce these enzymes. While this may be a potential mechanism, the authors do not comment on how long the patient received rifampin. Rifampin is also a CYP3A4 inducer and could have been parf of fhe reason for fhe decrease in quinidine level [46 ]. 

Cardiac glycosides have a small ratio of toxic to therapeutic concentration. Possible adverse effects are nausea, vomiting, abdominal pain, diarrhoea, fatigue, headache, drowsiness, colour vision disturbances, sinus bradycardia, premature ventricular complexes, AV-block, bigeminy, atrial tachycardia with AV-Block, ventricular fibrillation. There are several mechanisms relevant for their toxic action (Table 2). 

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